Arginine metabolism is profoundly altered by trauma and inflammation. The degradation of arginine by arginase is poorly understood. This application focusses on the regulation of arginine by arginase and has three aims. First, the investigator proposes to elucidate the roles of the two major isoforms, Arg I and Arg II, in the biosynthesis of NO, proline and polyamines in macrophages. The second aim is to elucidate the mechanisms regulating arginase expression in vivo. The third aim is to elucidate the physiologic roles of Arg II in vivo. The investigator will apply tools of modern molecular biology and genetics to address these questions.